{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:55:08Z","timestamp":1792086908042,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,10]],"date-time":"2019-03-10T00:00:00Z","timestamp":1552176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The present study evaluates the impact of hypoxia\u2010related carbonic anhydrase <jats:styled-content style=\"fixed-case\">IX<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">XII<\/jats:styled-content> isoenzyme expression as a basic adaptive mechanism to neutralise intracellular acidosis in classical Hodgkin's lymphoma (<jats:styled-content style=\"fixed-case\">cHL<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Eighty\u2010one primary biopsies and 15 relapsed tissue samples diagnosed with <jats:styled-content style=\"fixed-case\">cHL<\/jats:styled-content> were analysed for necrosis, <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CAXII<\/jats:styled-content> expression and cell proliferation to compare hypoxia\u2010related histological and functional data with survival characteristics. Variable, but highly selective cell membrane <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content> expression could be demonstrated in Hodgkin\u2013Reed\u2013Sternberg (<jats:styled-content style=\"fixed-case\">HRS<\/jats:styled-content>) cells in 39 of 81 samples (48.1%), while virtually no staining presented in their microenvironment. In contrast, <jats:styled-content style=\"fixed-case\">CAXII<\/jats:styled-content> expression in <jats:styled-content style=\"fixed-case\">HRS<\/jats:styled-content> cells could be demonstrated in only 18 of 77 samples (23.4%), with significant stromal positivity (50 of 77, 64.9%). The <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content><jats:sup>+<\/jats:sup> positive phenotype was strongly associated with lymphocyte depletion (four of four, 100%) and nodular sclerosis (29 of 51, 56.9%) subtypes. <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content>\/Ki\u201067 dual immunohistochemistry demonstrated suppressed cell proliferation in <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content><jats:sup>+<\/jats:sup> positive compared to <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content><jats:sup>\u2212<\/jats:sup> negative <jats:styled-content style=\"fixed-case\">HRS<\/jats:styled-content> cells (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Seventy\u2010two months\u2019 progression\u2010free survival (<jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>) was significantly lower for the <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content> positive group (0.192) compared with the <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content> negative group (0.771) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), while the overall survival (<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>) did not differ (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.097).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hypoxic stress\u2010related adaptation \u2013 highlighted by <jats:styled-content style=\"fixed-case\">CAIX<\/jats:styled-content> expression \u2013 results in cellular quiescence in <jats:styled-content style=\"fixed-case\">HRS<\/jats:styled-content> cells, potentially contributing to the short\u2010term failure of the standard chemotherapy in <jats:styled-content style=\"fixed-case\">cHL<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13808","type":"journal-article","created":{"date-parts":[[2019,1,12]],"date-time":"2019-01-12T13:13:51Z","timestamp":1547298831000},"page":"699-708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hypoxia\u2010related carbonic anhydrase <scp>IX<\/scp> expression is associated with unfavourable response to first\u2010line therapy\u00a0in classical Hodgkin's lymphoma"],"prefix":"10.1111","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2503-7451","authenticated-orcid":false,"given":"G\u00e1bor","family":"M\u00e9hes","sequence":"first","affiliation":[{"name":"Department of Pathology Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orsolya","family":"Matolay","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Beke","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Czenke","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m","family":"J\u00f3na","sequence":"additional","affiliation":[{"name":"Hematology Division Department of Internal Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia","family":"Milt\u00e9nyi","sequence":"additional","affiliation":[{"name":"Hematology Division Department of Internal Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1rp\u00e1d","family":"Ill\u00e9s","sequence":"additional","affiliation":[{"name":"Hematology Division Department of Internal Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Bedekovics","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Medicine University of Debrecen Debrecen Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02982639"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1495"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-428896"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.53.1194"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(196603)19:3<317::AID-CNCR2820190304>3.0.CO;2-O"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19820501)49:9<1848::AID-CNCR2820490918>3.0.CO;2-Y"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.127498"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-005-1413-7"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-2470"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2014.08.002"},{"key":"e_1_2_6_14_1","first-page":"400","article-title":"Carbonic anhydrase IX, a hypoxia induced catalytic component of the pH regulating machinery in tumors","volume":"4","author":"Sedlakova O","year":"2013","journal-title":"Front. 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